{"entity":{"id":"bpdcn","kind":"cancer","name":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN)","aka":[],"tldr":"Blastic plasmacytoid dendritic cell neoplasm is a rare aggressive leukaemia-like blood cancer of dendritic-cell precursors, a few hundred US cases a year, that often first appears as bruise-like skin lesions. Two CD123-directed drugs, tagraxofusp and pivekimab sunirine, are the first targeted therapies; allogeneic transplant in first remission is still the only route to long-term control.","summary":"BPDCN derives from plasmacytoid dendritic cell precursors, expresses CD4, CD56, CD123 (IL-3 receptor alpha), TCF4 and TCL1, and presents with skin lesions, marrow involvement and cytopenias, often evolving to a leukaemic phase. Historically it was treated with ALL- or AML-type chemotherapy with brief responses and a median survival around a year.\n\nTagraxofusp (CD123-directed IL-3/diphtheria toxin fusion) was the first BPDCN-specific drug (2018), with ~70% response in untreated patients and capillary leak syndrome as its signature toxicity. Pivekimab sunirine (CD123 ADC) was approved in 2026 (CADENZA). Venetoclax-based regimens and hyper-CVAD are alternatives, and allogeneic transplant in first remission is the only route to long-term survival. CNS prophylaxis is recommended because of frequent occult CNS involvement.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Blastic_plasmacytoid_dendritic_cell_neoplasm","links":[{"label":"Tagraxofusp pivotal (NEJM 2019)","url":"https://doi.org/10.1056/NEJMoa1815105"}],"tags":["gap-fill","haematologic","rare"],"related":["aml","all-leukemia"],"cancers":[],"sections":[],"technologies":["adc","allogeneic-hsct","cytokine-therapy"],"targets":["cd123","bcl2"],"drugs":["tagraxofusp","pivekimab-sunirine","venetoclax"],"companies":["abbvie","menarini"],"institutions":[],"pathways":["apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pemmaraju-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"BPDCN is very rare (a few hundred cases per year in the US); median age ~65-70, male predominance; skin lesions in most.","subtypes":["Skin-only presentation","Leukaemic / marrow-involving disease","Cases arising with or from CMML/MDS"],"biomarkers":["CD123, CD4, CD56, TCF4, TCL1 immunophenotype","Absence of MPO, lysozyme, CD3","MYC rearrangement (8q24)","TET2, ASXL1, ZRSR2 mutations","CSF examination"],"standardOfCare":[{"setting":"First line","approach":"Tagraxofusp (monitor albumin for capillary leak) or pivekimab sunirine (2026); alternatives hyper-CVAD or venetoclax-based regimens; CNS prophylaxis.","refs":["tagraxofusp","pivekimab-sunirine","venetoclax"],"guideline":{"nccn":"Category 2A (tagraxofusp)","version":"NCCN Guidelines: AML (BPDCN section)"}},{"setting":"Consolidation","approach":"Allogeneic HSCT in first complete remission for eligible patients; autologous transplant in selected cases (Japanese data).","refs":["allogeneic-hsct","autologous-stem-cell-transplant"]},{"setting":"Relapsed","approach":"Alternative CD123 agent, venetoclax combinations, clinical trials; prognosis poor.","refs":["venetoclax","pivekimab-sunirine"]}],"stateOfArt":["Two CD123-directed approvals (tagraxofusp 2018, pivekimab 2026) give a rare disease dedicated therapies.","Transplant in first remission remains essential for cure; response to CD123 agents makes more patients eligible.","BCL2 dependence makes venetoclax a rational partner."],"history":[{"year":2008,"title":"WHO names BPDCN","note":"Reclassified from 'CD4+/CD56+ haematodermic neoplasm' as a distinct entity.","refs":[]},{"year":2018,"title":"Tagraxofusp approved","note":"First CD123-targeted therapy and first drug approved for BPDCN.","refs":["tagraxofusp"]},{"year":2019,"title":"Tagraxofusp NEJM pivotal data (Pemmaraju)","refs":["tagraxofusp"]},{"year":2026,"title":"Pivekimab sunirine approved","note":"CD123 ADC (CADENZA), FDA May 2026.","refs":["pivekimab-sunirine"]}],"pipeline":["pivekimab-sunirine","venetoclax","allogeneic-hsct"],"openProblems":["No randomised trials; sequencing of CD123 agents unknown.","Capillary leak syndrome with tagraxofusp.","Relapse after transplant."],"parent":"leukaemia"},"route":"/cancers/bpdcn/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"langerhans-cell-histiocytosis","kind":"cancer","name":"Langerhans cell histiocytosis (LCH)","route":"/cancers/langerhans-cell-histiocytosis/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"cd123","kind":"target","name":"CD123","route":"/targets/cd123/"}],"drug":[{"id":"pivekimab-sunirine","kind":"drug","name":"Pivekimab sunirine","route":"/drugs/pivekimab-sunirine/"},{"id":"tagraxofusp","kind":"drug","name":"Tagraxofusp","route":"/drugs/tagraxofusp/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"},{"id":"menarini","kind":"company","name":"Menarini / Stemline","route":"/companies/menarini/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"}],"paper":[{"id":"paper-pemmaraju-n-engl-j-med","kind":"paper","name":"Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm","route":"/key-papers/paper-pemmaraju-n-engl-j-med/"}],"term":[{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"trial":[{"id":"nct03386513","kind":"trial","name":"Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN","route":"/trials/nct03386513/"}]}}